The compounds according to the invention are the derivatives and diastereomers of the active center of thymopoietin. However, while the known peptides Arg-Lys-Asp, Arg-Ly-Asp-Val (Hungarian patent specification No. 185,263) and Arg-Lys-Asp-Val-Tyr (Hungarian patent specification No. 183,579), considered to be the active center of thymopoietin, exert a significant immunostimulating effect [Drugs of the Future 11, 764 (1986); and Drugs of Today 22, 17 (1986)], the peptides according to the present invention show instead the opposite action.
It is known that the causes or accompanying syndromes of several diseases can be traced back to disturbances of the dynamical function of the immune system. Immunostimulants are used for healing of hereditary, native (after-birth or after-parturition, old age) and acquired immunodeficiency diseases (e.g. after infections and operations, AIDS, etc.). However, there exists a number of diseases or state which can be attributed to the increased or temporarily undesired function of the immune system resulting in the spontaneous modification of the defense mechanism of the organism. In autoimmune diseases, the defense system is not capable of distinguishing the "own" from the "exogenous," thus, it protects itself by producing antibodies against its own antigen too, whereby severe consequences occur. Allergy diseases are accompanied by an increased production of antibodies caused by exogenous substances. The rejecting reaction following organ transplants is also a consequence of the normal and healthy function of the organism which, however, should temporarily by suspended for allowing the transplanted foreign organ to be built into the organism.
Cyclophosphamide [2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide], azathioprin [6-(1-methyl-4-nitro-5-imidazolylthio)purine] and corticosteroids used for treating the autoimmune diseases as well as H-1 receptor-blocking antihistamines used for treating allergies, and cyclosporin, being an indispensable drug for organ transplants belong to the immunosuppressive agents inhibiting the increased function or weakening the normal function of the immune system.
A number of accompanying side effects can be explained by the relatively low therapeutic index (&lt;10) of the immunosuppressive drugs. Thus, they can be administered only under exact medical control and, in general, only for a limited period. A particular advantage of the peptide-type active agents consists in their extraordinarily high therapeutic index (&gt;100 to 1000), i.e. their dose inducing a harmful effect is several orders of magnitude higher than their effective dose; under physiological conditions, they are very rapidly decomposed and do not accumulate in the organism. Their effect is based on their ability to undergo complicated reactions with a high efficiency during their short life.